Inhibitory effect of metals on animal and plant glutathione transferases

Dobritzsch, Dirk; Grancharov, Konstantin; Hermsen, Corinna; Krauss, Gerhard; Schaumlöffel, Dirk

doi:10.1016/j.jtemb.2019.09.007

Cited by 47 publications

(22 citation statements)

References 104 publications

(108 reference statements)

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“…A key strategy is to compartmentalize ROS, to limit their levels by balancing generation with antioxidative mechanisms, and to control their diffusion capacity. TMs do not only participate in ROS generation as detailed above but can also influence antioxidative capacity, such as by exhausting glutathione supply, inhibiting or damaging antioxidative enzymes, altering protein structure and conformation, and influencing synthesis or regeneration of antioxidants (Dobritzsch et al 2020 ; Limon-Pacheco and Gonsebatt 2009 ). Consequently, physiological ROS can be impacted through disruption, diversion or ablation of the signaling pathway.…”

Section: Transition Metals: Environmental Presence Exposure General M...mentioning

confidence: 99%

Renal hypoxia–HIF–PHD–EPO signaling in transition metal nephrotoxicity: friend or foe?

2022

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The kidney is the main organ that senses changes in systemic oxygen tension, but it is also the key detoxification, transit and excretion site of transition metals (TMs). Pivotal to oxygen sensing are prolyl-hydroxylases (PHDs), which hydroxylate specific residues in hypoxia-inducible factors (HIFs), key transcription factors that orchestrate responses to hypoxia, such as induction of erythropoietin (EPO). The essential TM ion Fe is a key component and regulator of the hypoxia–PHD–HIF–EPO (HPHE) signaling axis, which governs erythropoiesis, angiogenesis, anaerobic metabolism, adaptation, survival and proliferation, and hence cell and body homeostasis. However, inadequate concentrations of essential TMs or entry of non-essential TMs in organisms cause toxicity and disrupt health. Non-essential TMs are toxic because they enter cells and displace essential TMs by ionic and molecular mimicry, e. g. in metalloproteins. Here, we review the molecular mechanisms of HPHE interactions with TMs (Fe, Co, Ni, Cd, Cr, and Pt) as well as their implications in renal physiology, pathophysiology and toxicology. Some TMs, such as Fe and Co, may activate renal HPHE signaling, which may be beneficial under some circumstances, for example, by mitigating renal injuries from other causes, but may also promote pathologies, such as renal cancer development and metastasis. Yet some other TMs appear to disrupt renal HPHE signaling, contributing to the complex picture of TM (nephro-)toxicity. Strikingly, despite a wealth of literature on the topic, current knowledge lacks a deeper molecular understanding of TM interaction with HPHE signaling, in particular in the kidney. This precludes rationale preventive and therapeutic approaches to TM nephrotoxicity, although recently activators of HPHE signaling have become available for therapy.

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Section: Transition Metals: Environmental Presence Exposure General M...mentioning

confidence: 99%

Renal hypoxia–HIF–PHD–EPO signaling in transition metal nephrotoxicity: friend or foe?

2022

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“…The most significant reduction of enzyme activity compared to levels from Vacaresti Lake was noticed for GST activity in the gut of fish from Chitila, Floreasca and Tei lakes, the level being at 17%, 21% and 13%, respectively, of that recorded in fish from Vacaresti Lake. Having an important role in detoxification, these low levels of GST might suggest an inhibition of the this enzyme’s activity, most likely explained by the high level of several heavy metals (Cr, Cu, Fe, Ni and Fe) ( Table 2 ) that accumulated in the gut of fish found in Chitila, Floreasca and Tei lakes compared to the fish living in the protected environment of Vacaresti Lake [ 36 , 37 ].…”

Section: Resultsmentioning

confidence: 99%

Antioxidative Defense and Gut Microbial Changes under Pollution Stress in Carassius gibelio from Bucharest Lakes

Pelcaru

Nica

Niță-Lazăr

et al. 2022

IJERPH

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Fish are able to accumulate by ingestion various contaminants of aquatic environment, with negative consequences on their intestine, being continuously threatened worldwide by heavy metals, pesticides and antibiotics resulted from the human activities. Consequently, the health of other species can be affected by eating the contaminated fish meat. In this context, our study aimed to perform a comparison between the changes in intestine samples of Carassius gibelio individuals collected from different artificial lakes in Bucharest (Romania), used by people for leisure and fishing. The presence of various metals, pesticides and antibiotics in the gut of fish was assessed in order to correlate their accumulation with changes of antioxidative enzymes activities and microbiome. Our results showed that fish from Bucharest lakes designed for leisure (Chitila, Floreasca and Tei lakes) have an increased level of oxidative stress in intestine tissue, revealed by affected antioxidant enzymes activities and GSH levels, as well as the high degree of lipid peroxidation, compared to the fish from protected environment (Vacaresti Lake). Some heavy metals (Fe, Ni and Pb) and pesticides (aldrin and dieldrin) were in high amount in the gut of fish with modified antioxidative status. In conclusion, our study could improve the knowledge regarding the current state of urban aquatic pollution in order to impose several environmental health measures.

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“…In addition to enzymatic functions, Gsts play a role in the modulation of signal transduction pathways involved in cell survival and apoptosis via protein-protein interactions, where they control the activity of the MAPK family members (Allocati et al, 2018). Metals including Ag + have been shown to inhibit the activity of Gsts (Dobritzsch et al, 2019). One of the possible implications of AgNP-mediated downregulation of Gst genes in the liver is an increased susceptibility to carcinogens, drugs and noxious chemicals.…”

Section: Discussionmentioning

confidence: 99%

Surface coatings alter transcriptional responses to silver nanoparticles following oral exposure

et al. 2020

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Silver nanoparticles (AgNPs) are used in food packaging materials, dental care products and other consumer goods and can result in oral exposure. To determine whether AgNP coatings modulate transcriptional responses to AgNP exposure, we exposed mice orally to 20 nm citrate (cit)-coated AgNPs (cit-AgNPs) or polyvinylpyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) at a 4 mg/kg dose for 7 consecutive days and analyzed changes in the expression of protein-coding genes and long noncoding RNAs (lncRNAs), a new class of regulatory RNAs, in the liver. We identified unique and common expression signatures of protein-coding and lncRNA genes, altered biological processes and signaling pathways, and coding-non-coding gene interactions for cit-AgNPs and PVP-AgNPs. Commonly regulated genes comprised only about 10 and 20 percent of all differentially expressed genes in PVP-AgNP and cit-AgNP exposed mice, respectively. Commonly regulated biological processes included glutathione metabolic process and cellular oxidant detoxification. Commonly regulated pathways included Keap-Nrf2, PPAR, MAPK and IL-6 signaling pathways. The coding-non-coding gene co-expression analysis revealed that proteincoding genes were co-expressed with a variable number of lncRNAs ranging from one to twenty three and may share functional roles with the protein-coding genes. PVP-AgNP exposure induced a more robust transcriptional response than cit-AgNP exposure characterized by more than twofold higher number of differentially expressed both protein-coding and lncRNA genes. Our data demonstrate that the surface coating strongly modulates the spectrum and the number of

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Inhibitory effect of metals on animal and plant glutathione transferases

Cited by 47 publications

References 104 publications

Renal hypoxia–HIF–PHD–EPO signaling in transition metal nephrotoxicity: friend or foe?

Renal hypoxia–HIF–PHD–EPO signaling in transition metal nephrotoxicity: friend or foe?

Antioxidative Defense and Gut Microbial Changes under Pollution Stress in Carassius gibelio from Bucharest Lakes

Surface coatings alter transcriptional responses to silver nanoparticles following oral exposure

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